Revised_Supplementary_Material_db19-1256.docx (22.59 kB)
Download fileCentral KATP channels modulate glucose effectiveness in humans and rodents
figure
posted on 2020-05-01, 15:25 authored by Ada AdminAda Admin, Michelle Carey, Eric Lontchi-Yimagou, William Mitchell, Sarah Reda, Kehao Zhang, Sylvia Kehlenbrink, Sudha Koppaka, Sylvan Roger Maginley, Sandra Aleksic, Shobhit Bhansali, Derek M. Huffman, Meredith HawkinsHyperglycemia
is a potent regulator of endogenous glucose production (EGP). Loss of this
‘glucose effectiveness’ is a major contributor to elevated plasma glucose
concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (KATP
channels) in the central nervous system (CNS) have been shown to regulate EGP
in humans and rodents. We examined the contribution of central KATP
channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic
clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic
humans and normal Sprague Dawley rats. By contrast, antagonism of KATP
channels with glyburide significantly reduced the EGP-lowering effect of
hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on
EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular
(ICV) administration of the KATP channel agonist diazoxide. These findings
indicate that about half of EGP suppression by hyperglycemia is mediated by
central KATP channels. These central mechanisms may offer a novel
therapeutic target for improving glycemic control in T2D.